Diseases, Disorders and Injury of the CNS
Diseases, disorders and injury of the CNS affect millions of people worldwide. With an increase in lifespan and changing population demographics, the incidence of CNS diseases is expected to increase significantly in the 21st century. The delivery of therapeutic oligonucleotide compounds to the CNS for effective treatment of CNS diseases, disorders and injury present a major challenge. For therapeutic purpose, it is important to consider not only the net delivery of a nucleic acid compounds to the CNS, but also the ability of the therapeutic oligonucleotide to access the relevant target site within the CNS.
Hitherto, the main approaches to delivery of oligonucleotide compounds to the CNS have been systemic administration, injection into cerebrospinal fluid (CSF) pathways and direct injection into the brain. For instance, modulation of the expression of certain genes involved in Alzheimer's diseases (AD), as well as that of genes involved in Huntington's disease has been attained in vivo by intrathecal and intracerebroventricular administration, implantation of catheters and pumps, by chemical or osmotic opening of the blood-brain barrier, by direct injection or perfusion at the site of injury or lesion, or by direct injection or perfusion into the arterial system of the brain (see for example WO 2005/003350, US 20050042646 and GB 2415961).
Intranasal administration of therapeutic oligonucleotide compounds for the treatment of CNS diseases has been described in WO 02/086105 and WO 2007/107789.
There remains a need for an effective method for delivery of therapeutic oligonucleotides to the CNS useful in treating diseases, disorders and injury of the CNS.